Collagen is a protein which occurs naturally in all animals in the form of tough fibers. Such collagen fibers are in effect the "glue" holding together the tissues of the body. Collagen is synthesized by many cells from certain amino acid including the amino acid proline. Collagen-producing cells are located primarily in the skin, bone, tendons, ligaments, nerves, cartilage and blood vessels of animals and collagen fibers are formed whenever tissue is damaged, in the sense that deposition of collagen fibers is a normal part of the process of tissue repair. In certain instances, however, excessive amounts of collagen are produced, with substantial, undesirable results. In particular, scar formation in the healing of wounds, from trauma or disease, or following surgery, is a result of excessive production of collagen, since the major constituent of scar tissue is collagen.
The development of large, unsightly masses of scar tissue may produce psychological problems in human beings, and may interfere substantially with the normal physical and biological function of organs and tissues. For example, after surgery to the abdomen, the formation of excessive scar tissue or "adhesions" around abdominal organs, such as the intestines, often interferes with the functionality of such organs and may cause severe pain and even death. After hand surgery, the formation of excessive scar tissue around the tendons of the wrist or hand often prevents normal functioning of the hand. After surgery to the back, excessive scar tissue around the spinal nerves may produce severe pain and limitation of motion. After plastic surgery to the face, the formation of excessive scar tissue may frequently compromise the benefits of the surgery.
In horses, a condition known as "proud flesh" often occurs. It is an excessive build-up of scar tissue and when occuring near a leg joint may interfere considerably with the use of the legs for heavy work or for racing. Similar excessive build-up of scar tissue may also occur in horses when leg tendons are surgically repaired.
It is, therefore, desirable to be able to control or limit the amount of collagen formed and released by the collagen-producing cells in specific body areas for limited periods of time. However, in controlling the synthesis and depositon of collagen fibers, it is extremely important not to interfere with the cellular production of other protein necessary for normal body functioning.
In Belgian Pat. No. 784650, there is disclosed the use of free proline analogs in a pharmaceutically acceptable carrier for controlling collagen formation. The use of such proline analog exhibited some efficacy in reducing scar tissue formation, however, the benefit was at best minimal. Such free proline analogs are not susceptible to topical application about a wound, since topical application results in an edematose condition, i.e. the accumulation of fluid with concomitant symptoms of pain and swelling. Further, free proline analogs are water soluble and readily absorbed thereby entering the circulation system.